| Abstract: | The recent recognition of complex and chronic phenotypes of T cell–mediated rejection (TCMR) has fostered the need to better evaluate the response of acute TCMR—a condition previously considered to lack relevant consequences for allograft survival—to the standard of care. In a prospective cohort of kidney recipients (n = 256) with biopsy‐proven acute TCMR receiving corticosteroids, we investigated clinical, histological, and immunological phenotypes at the time of acute TCMR diagnosis and 3 months posttreatment. Independent posttreatment determinants of allograft loss included the glomerular filtration rate (GFR) (HR = 0.94; 95% CI = 0.92‐0.96; P < .001), proteinuria (HR = 1.40; 95% CI = 1.10‐1.79; P = .007), time since transplantation (HR = 1.02; 95% CI = 1.00‐1.03; P = .016), peritubular capillaritis (HR = 2.27; 95% CI = 1.13‐4.55; P = .022), interstitial inflammation in sclerotic cortical parenchyma (i‐IF/TA) (HR = 1.87; 95% CI = 1.08‐3.25; P = .025), and donor‐specific anti‐HLA antibodies (DSAs) (HR = 2.67; 95% CI = 1.46‐4.88; P = .001). Prognostic value was improved using a composite evaluation of response to treatment versus clinical parameters only (cNRI = 0.68; 95% CI = 0.41‐0.95; P < .001). A classification tree for allograft loss identified five patterns of response to treatment based on the posttreatment GFR, i‐IF/TA, and anti‐HLA DSAs (cross‐validated accuracy = 0.80). Compared with responders (n = 155, 60.5%), nonresponders (n = 101, 39.5%) had a higher incidence of de novo DSAs, antibody‐mediated rejection, and allograft loss at 10 years (P < .001 for all comparisons). Thus, clinical, histological, and immunological assessment of response to treatment of acute TCMR revealed different profiles of the response to treatment with distinct outcomes. |
